JP2018094435A - Drug filled delivery assembly - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide a system and device configured to help a user in the administration of two or more drugs in an efficient, simple, safe and reliable way.SOLUTION: A drug delivery assembly 100 comprises a housing 110, a piston 120 axially displaceable in the housing 110, and a variable volume reservoir 105 formed by the housing 110 and the piston 120 and containing a first fluid drug. The assembly 100 further comprises an exterior fluid inlet 150 arranged in or configured to be arranged in fluid communication with the reservoir 105, a fluid outlet 145 arranged in or configured to be arranged in fluid communication with the reservoir, biasing means configured for moving the piston 120 forwards, and releasable retaining means 113 configured for retaining the piston 120 in an initial position.SELECTED DRAWING: Figure 2

Description

  The present invention generally relates to a filled drug delivery assembly adapted for use in combination with a drug delivery device. In a specific embodiment, the present invention relates to a drug delivery system configured to deliver two or more drugs through a common medication interface.

  In the present disclosure, reference is primarily made to the treatment of diabetes, but this is merely an exemplary application of the invention.

  Drug injection devices have greatly improved the lives of patients who must self-administer drugs and biologics. The drug injection device can take a variety of forms, including a simple disposable device which is not much different from an ampoule with injection means, or they can be electrically controlled devices with many highly elaborate functions. is there. Whatever its form, they have proven to be of great help in helping patients self-administer injectable drugs and biologics. They also greatly help caregivers to administer injectable medications to people who are unable to perform self-injections.

  For optimal treatment for certain diseases and / or certain disease states, it may be necessary to administer more than one drug. For example, a long-acting insulin formulation and a GLP-, for example, liraglutide marketed as Victoza®, or exenatide marketed as Byetta® or long-acting Bydureon®. It may be beneficial to treat patients with subcutaneous administration of both GLP-1 (glucagon-like peptide-1) -based formulations, such as one analog.

  There are a number of potential problems when delivering two active drug substances simultaneously. In complex liquid formulations, two types of drug substances can interact during long shelf life storage. Thus, it may be advantageous to store the active ingredients separately and mix them for the first time at the time of delivery, for example by injection, needle-free injection, pump, inhalation and the like. However, the process of administering the two types of drugs needs to be simple and easy for the user to perform reliably and repeatedly.

  Yet another problem is that the amount of each drug substance that forms a combination therapy may need to be changed for each user or for different stages of each user's therapy. For example, one or more drugs may require a titration period to gradually introduce the patient to a normal dose. Yet another example is where one formulation requires a fixed dose that does not require adjustment and the other varies depending on the patient's condition or physical condition. The problem is that a formulation in which a plurality of active drug substances are premixed is not appropriate because the premixed formulation has a fixed ratio of active ingredients that cannot be changed by a healthcare professional or user. Means there is.

  Many users have to use more than one drug delivery system when multiple drug therapies are required, or when the exact calculations required for the required dose combination must be made Yet another problem can arise because it can be difficult. In response to this problem, fixed dose medicinal modules adapted to be mounted on variable dose delivery devices have been proposed, see for example WO 2011/117284 and WO 2011/117287. I want to be.

  In view of the above, an object of the present invention is to provide a system and apparatus configured to help a user administer two or more drugs in an efficient, simple, safe and secure manner. . Yet another object is a fluid delivery device comprising a first drug, which can administer another drug through a common fluid outlet, and that does so in an efficient, simple, safe and reliable manner. Is to provide.

  In the present disclosure, embodiments and aspects are addressed that address one or more of the above objects, or that address objects that are apparent from the following disclosure and from the description of exemplary embodiments.

  That is, according to the first aspect of the present invention, the variable volume type formed by the housing, the piston that is axially displaceable in the housing, the housing and the piston, and in the initial state contains the first fluid medicine. A drug delivery assembly is provided comprising a reservoir. The assembly is disposed in fluid communication with the reservoir or configured to be disposed in fluid communication, and is configured to be disposed in fluid communication with the reservoir or configured to be in fluid communication. The fluid outlet, the displacement means for moving the piston forward, and the releasable holding means for holding the displacement means in the biased state, and when the holding means is released, The piston can be moved forward to release fluid medication from the reservoir. “External” defines a fluid inlet configured to be placed in fluid communication with an external fluid supply.

  In this way, the fluid inlet can be placed in fluid communication with the fluid outlet of the drug delivery device comprising the second fluid drug, and two types of drugs can be released through the fluid outlet of the drug delivery assembly. The fluid outlet serves as a common fluid outlet for the two types of drugs. In this way, separate storage reservoirs of two or more active agents can be combined and the agents are delivered to the patient in a single delivery procedure. Furthermore, by using a variable volume reservoir, it is possible to avoid that the first drug is simply replaced by the second drug, which allows a more accurate dose of the second drug. Realize. The holding means can serve to hold the piston in its initial position, for example by preventing the piston from moving or by suppressing the action of the biasing means on the piston in the initial biased state. .

  Thus, setting the dose of one drug does not automatically fix or determine the dose of the other drug (ie, a drug that cannot be set by the user). In addition, an opportunity to change the amount of one or both agents can be obtained. For example, the amount of one fluid can be varied by changing the characteristics of the injection device (eg, dialing a user variable dose or changing the “fixed” dose of the device). The amount of the second fluid can be varied by manufacturing a variety of second drug containment assemblies, each variant containing a different volume and / or concentration of the second drug. The user or health care worker will then select the second assembly or series of various assemblies most appropriate for the particular therapy.

  The displacement means can be configured to be moved from the initial state to the biased state by a user operation. The biasing means can take the form of, for example, a spring that can be slightly compressed in the initial state, for example to prevent backlash, but the energy stored in the initial state is in contrast to the biased state, It is not enough to completely empty the reservoir. Alternatively, the assembly can be provided with pre-biased biasing means.

  The drug delivery assembly is attached to a drug delivery device comprising a second reservoir containing a second fluid drug and a coupling means configured to attach to a corresponding coupling means disposed on the drug delivery assembly. When the coupling means are coupled together, the fluid inlet is placed in fluid communication with the second reservoir and the deflection means is moved from the initial state to the biased state. Alternatively, the deflection means can be moved by independent means.

  In an exemplary embodiment of the drug delivery assembly, the fluid outlet is energized by an initial state where there is no fluid communication between the fluid outlet and the reservoir and by the presence of fluid communication between the fluid outlet and the reservoir. The biasing means has an operating condition that allows the piston to move forward to release fluid medicament from the reservoir through the fluid outlet.

  In order to be able to control the flow of fluid through the assembly, the fluid inlet is in an initial state where there is no fluid communication between the fluid inlet and the reservoir, and there is fluid communication between the fluid inlet and the fluid outlet. With existing operating conditions. To form fluid communication, the piston comprises a fluid conduit (e.g., a lumen) in fluid communication with the fluid inlet, and the piston is from an initial position where there is no fluid communication between the fluid conduit and the fluid outlet. It is possible to move to a connection position where fluid communication is formed between the fluid outlet and the fluid conduit and thus between the fluid inlet and the fluid outlet.

  The reservoir may comprise a region through which the needle can pass, and the fluid outlet is a distal hollow needle that is axially displaceable between an initial position and an actuated position, wherein the fluid outlet and reservoir are in the initial position. There is no fluid communication between them, and in the activated position, the distal hollow needle is disposed through the needle penetrable region to be in fluid communication with the reservoir, thereby providing biased biasing means. , Can take the form of a distal hollow needle that allows the piston to move forward to release fluid drug from the reservoir through the distal hollow needle.

  The proximal portion of the distal hollow needle can project into the reservoir in its activated position, and the piston can comprise an area through which the needle can penetrate. The fluid inlet is a proximal hollow needle having a distal portion disposed within the piston conduit and in fluid communication with the piston conduit when the piston moves axially from its initial position to its connected position, In position, the proximal portion of the distal hollow needle can take the form of a proximal hollow needle that is placed in fluid communication with the proximal hollow needle by being disposed through the needle penetrable region of the piston. . This arrangement allows fluid communication to be established between the distal hollow needle and the proximal hollow needle via the piston conduit.

  In a further aspect of the present invention there is provided a medical assembly comprising the above-described drug delivery assembly in combination with a drug delivery device, the drug delivery device comprising a second reservoir containing a second fluid drug, and a dose. A release assembly for releasing the drug from the second reservoir and a coupling means. The drug delivery assembly further comprises corresponding coupling means configured to attach to the coupling means of the drug delivery device so that when the coupling means are coupled together, the fluid inlet is in fluid communication with the second reservoir. Placed in.

  In yet another embodiment, the retaining means is configured to be released when fluid is introduced into the reservoir via the fluid inlet, thereby fluid introduced into the reservoir via the fluid inlet. When the piston moves backward, the displacement means can be released.

  The drug delivery assembly includes a proximal end forming a fluid inlet, a distal end forming a fluid outlet, an intermediate opening disposed in fluid communication with the reservoir, or configured to be disposed in fluid communication. A hollow needle having The hollow needle can be disposed through the piston, and the sealing portion is provided between the piston and the hollow needle so that the piston is axially rearward (proximal direction) and forward of the hollow needle. (Distal direction). The hollow needle can be arranged to have an initial position and an operating position, where the intermediate opening is placed in sealing engagement with the piston, and in the operating position, the intermediate opening is in fluid communication with the reservoir. Placed in.

  The drug delivery assembly can be configured to be attached to a drug delivery device comprising a second reservoir containing a second fluid drug, the drug delivery device comprising second coupling means, the drug delivery assembly comprising: First coupling means configured to attach to the second coupling means is provided. When the first coupling means and the second coupling means are coupled to each other, the fluid inlet is disposed in fluid communication with the second reservoir, and the hollow needle moves to its operating position, whereby the second reservoir Fluid communication is established between the reservoir of the drug delivery assembly and between the reservoir of the drug delivery assembly and the fluid outlet. A one-way valve may be provided to prevent fluid flow from the reservoir to the fluid inlet.

  In yet another aspect of the present invention, a drug delivery assembly of the type described above having an actuatable hollow needle, a second reservoir containing a second fluid drug, and releasing a quantity of drug from the second reservoir. A medical assembly is provided comprising a release assembly, a spring means for driving the release assembly, and a drug delivery device comprising a second coupling means. The drug delivery assembly further comprises first coupling means configured to attach to the second coupling means, wherein the coupling means couples the first coupling means and the second coupling means to each other. An inlet is disposed in fluid communication with the second reservoir, and the hollow needle is moved to its operating position so that the second reservoir and the reservoir of the drug delivery assembly, as well as the reservoir and fluid outlet of the drug delivery assembly, Fluid communication is established, wherein the deflection means is configured to generate a first pressure in the reservoir of the drug delivery assembly and the spring means is higher in the second reservoir. It is configured to generate pressure, thereby preventing fluid flow from the reservoir of the drug delivery assembly to the fluid inlet.

  Alternatively, the spring means can be configured to generate a lower second pressure in the second reservoir so that the drug is first completely released from the reservoir of the assembly via the needle. The piston moves forward until it is delivered, after which the drug is released from the cartridge. In practice, this may require that no drug can flow from the assembly reservoir back through the intermediate opening and into the cartridge. One way to prevent this is to prevent fluid flow from the reservoir to the fluid inlet, for example by a unidirectional coupling that prevents the piston rod from being pushed back, as in FlexTouch® from Novo Nordisk, for example. Relying on a delivery device provided with one-way means to do this. Alternatively, the delivery assembly can be provided with a one-way valve that prevents fluid flow from the reservoir to the fluid inlet.

  In yet another exemplary embodiment, the reservoir is initially pressurized by the deflection means. When the fluid outlet is in an initial state where there is no fluid communication between the fluid outlet and the reservoir, and the fluid communication between the fluid outlet and the reservoir causes the piston to move forward to the displacement means, An actuating state that allows the drug to be released from the reservoir through the fluid outlet, and the fluid inlet is in an initial state where there is no fluid communication between the fluid inlet and the reservoir, and between the fluid inlet and the fluid outlet. And an operating state in which fluid communication exists. The fluid outlet has a surface adapted to press against the skin surface and can be coupled to a trigger member that is movable relative to the housing so that the trigger member presses against the user's skin surface. When done, the fluid outlet can be moved to an operating position that is in fluid communication with the reservoir.

  The piston may be provided with a fluid conduit in fluid communication with the fluid inlet, the piston from the initial position where there is no fluid communication between the fluid conduit and the fluid outlet, between the fluid outlet and the fluid conduit, It is thus possible to move to a connection position where fluid communication is formed between the fluid inlet and the fluid outlet via the fluid conduit.

  The reservoir may be provided with a region through which the needle can pass, and the fluid outlet is a distal hollow needle that is displaceable between an initial position and an operating position, wherein the fluid outlet and reservoir are in the initial position. There is no fluid communication between them, and in the activated position, the distal hollow needle may take the form of a distal hollow needle that is placed in fluid communication with the reservoir by being placed through the needle penetrable region. it can.

  The proximal portion of the distal hollow needle can be arranged to project into the reservoir in its activated position, and the piston comprises a region through which the needle can penetrate. The fluid inlet is a proximal hollow needle having a distal portion disposed within the piston conduit and in fluid communication with the piston conduit when the piston moves axially from its initial position to its connected position, In position, the proximal portion of the distal hollow needle can take the form of a proximal hollow needle that is placed in fluid communication with the proximal hollow needle by being disposed through the needle penetrable region of the piston. .

  In yet another aspect, the delivery assembly comprises user-actuated release means configured to release the holding means when actuated. The user actuated release means may comprise a sliding needle protector that initially covers the distal needle, the needle protector being pushed proximally when the assembly is pressed against the skin surface by the user. . Since the needle protector can be spring biased, the needle protector automatically moves in the distal direction to cover the distal needle when the assembly is pulled back from the skin surface. The needle protector can also be used to form a lock such that the assembly cannot be released until the needle protector is pushed proximally. With respect to the design with the actuated needle mechanism described above, this allows the user to “empty” the delivery device, ie, let air escape from the needle before inserting the distal needle subcutaneously.

  As used herein, the term “medicament” can be controlled through a delivery means such as a cannula or hollow needle, such as a liquid, solution, gel or fine suspension containing one or more drugs. It is meant to encompass any fluid medical formulation. Exemplary agents include peptides (eg, insulin, insulin-containing agents, GLP-1 containing agents and derivatives thereof), proteins, hormones, biological derivatives or active agents, hormones and gene-based agents, nutritional formulas, As well as other substances in both solid (dispensed) or liquid form. In the description of the exemplary embodiments, reference is made to the use of insulin and GLP-1-containing drugs, including analogs thereof and combinations with one or more other drugs. Correspondingly, the term “subcutaneous” delivery is meant to encompass any method of transdermal delivery to a subject.

  In the following, the present invention will be further described with reference to the drawings.

It is a figure of embodiment of a chemical | medical agent delivery apparatus. 1 is a cross-sectional view of a first embodiment of a pre-filled delivery assembly. FIG. FIG. 3 is a cross-sectional view of an alternative form of the embodiment of FIG. FIG. 3 is a diagram of the embodiment of FIG. 2 in various usage states. FIG. 3 is a diagram of the embodiment of FIG. 2 in various usage states. FIG. 3 is a diagram of the embodiment of FIG. 2 in various usage states. FIG. 3 is a diagram of the embodiment of FIG. 2 in various usage states. FIG. 3 is a diagram of the embodiment of FIG. 2 in various usage states. FIG. 3 is a diagram of the embodiment of FIG. 2 in various usage states. 4B is a view from different viewing angles corresponding to FIGS. 4A and 4C. FIG. 4B is a view from different viewing angles corresponding to FIGS. 4A and 4C. FIG. FIG. 6 is a cross-sectional view of a second embodiment of a pre-filled delivery assembly. It is a figure of one element of 2nd Embodiment. 6B is a diagram of the embodiment of FIG. 6B is a diagram of the embodiment of FIG. 6B is a diagram of the embodiment of FIG. 6B is a diagram of the embodiment of FIG. FIG. 6 is a third embodiment of a pre-filled delivery assembly.

  In the figures, the same structures are indicated primarily by the same reference numerals.

  In the following, when terms such as "upper" and "lower", "right" and "left", "horizontal" and "vertical" or similar related expressions are used, they are for the attached drawings only It does not refer to the actual state of use. The figures shown are schematic representations, and therefore the various structural configurations and their associated dimensions serve exemplary purposes only.

  Referring to FIG. 1, a pen type drug delivery device 1 is depicted. This device represents a “generic” drug delivery device that presents examples of devices that are intended to use embodiments of the present invention in combination. More specifically, the pen device comprises a cap part (not shown) and a main part 2, which comprises a proximal part 10 in which a drug release mechanism is disposed, and a needle. A transparent cartridge 21 filled with medicament, having a distal septum 23 through which can be penetrated, is held therein in place by a cartridge holding device 22 disposed therein and mounted proximally. A distal reservoir portion 20 and the cartridge holding device has an opening through which a portion of the cartridge can be inspected. The device can be disposable and can be pre-loaded with a cartridge that is not intended to be removed, or it can be designed to be loaded with a new cartridge by the user. The cartridge comprises a piston driven by a piston rod that forms part of the release mechanism. The proximal rotary dose ring member 12 serves to manually set the desired dose of the drug shown in the display window 15, and that desired dose is released when the release button 13 is actuated. Can do. Depending on the type of drug release device, the release mechanism may comprise a spring that is deformed during dose setting and is released when the release button 13 is actuated to drive the piston rod. Alternatively, the release mechanism can be completely manual, in which case the dose ring member 12 and release button 13 move proximally during dose setting, corresponding to the set dose size, It is then moved in the distal direction to release a set dose. The cartridge (or alternatively the cartridge holding device) comprises a distal coupling means in the form of a needle hub mount 25, which in the illustrated example is within the hub of the corresponding needle assembly (see below). It has an external thread adapted to engage a screw or bayonet as well as a bayonet. When using the above general type of drug delivery device (which has other shape elements and can also be provided with a powered release mechanism), the user performs a subcutaneous injection by performing the following steps: Is usually recommended. That is, the cap is removed to expose the needle mount, a new needle assembly is mounted, the dose to be released is set by rotating the dose setting member, and when the needle is inserted subcutaneously, the drug release means Actuate the release means to drive or release to release the set dose, remove the needle assembly from the needle mount after removing the needle from the skin, and reattach the cap to cover the needle mount.

  FIG. 2 schematically illustrates, in an initial state, a first embodiment of a pre-fillable delivery assembly 100 comprising a housing 110, a piston assembly 120, a drive assembly 130, a distal needle assembly 140, and a proximal hollow needle 150. Indicate. A generally cylindrical housing 110 defines a general axis of the assembly, a distal wall 111 having a central opening 112 within which a reservoir septum 113 is piercable by a needle, and a distal wall disposed about the central opening. A proximal wall portion 116 (FIG. 5B) having a tubular portion 114 extending in a lateral direction, an outer skirt portion 115 extending in a distal direction, and a central opening 117 about which four quadrant openings are disposed. And a circumferential coupling means 119 (eg internal thread or bayonet as shown) on the inner surface that allows the assembly to be attached to a corresponding hub mount of, for example, the drug delivery device shown in FIG. And a skirt portion 118 extending in the direction. Between the two walls, an internal cavity 105 is formed which is filled with a liquid formulation in the initial sealed state. The illustrated housing is assembled from two parts corresponding to the circumferential division 106 arranged between the two walls, so that components can be mounted in the cavity during assembly. .

  The piston assembly 120 is axially displaceable within the cavity and in the illustrated embodiment comprises a first portion 121 and a supporting second portion 127, although the piston is a single element. Can also be manufactured. The first portion comprises a disc portion having a piston surface 122 facing distally and a circumferential skirt portion 123 extending in a proximal direction in sliding and sealing engagement with the inner wall portion of the housing. And a variable volume reservoir is formed between the distal wall, the piston face, and the housing. The first portion further comprises a proximally extending lumen 124 having a proximal and distal aperture and an axial lumen 125 having a plurality of circumferential constrictions 153, through which the needle can pass. A piston septum 126 is located distally. The second portion includes a cylindrical shaft 128 that surrounds and engages the lumen and a distal circumferential flange 129 that engages and supports the disc of the piston.

  The drive assembly 130 includes a spring load member 131 and a helical coil spring 132. The spring-loaded member includes a proximal disc portion 133 having a central opening in which a proximal partition wall 134 through which the needle can pass is disposed, and four pieces each having a substantially circular shape and extending in the distal direction. , And the inner surface of the leg is in sliding and supporting engagement with the cylindrical shaft 128. The distal portion of each leg includes a flange 135 that extends laterally and also has a substantially quadrant. In the initial state shown in FIG. 4A, the disc portion 133 is positioned away from the proximal wall and the four legs extend distally through the corresponding four quadrant openings in the proximal wall portion. Yes. Because the flange 135 extends laterally relative to the opening, the spring-loaded member is secured to the housing by the proximally-facing flange surface abutting the proximal wall, and the spring-loaded member is further Allows movement in the distal direction. The coil spring 122 is concentrically arranged around the shaft portion with the distal end supported by the piston flange portion and the proximal portion supported by the leg flange. In the initial state, the piston is under light compression, which locks the spring-loaded member in the nearest initial position because the piston cannot move distally by a reservoir filled with liquid and sealed. Produces a proximally directed force.

  The proximal hollow needle 150 is fixedly disposed within the central opening 116 in the proximal wall and is proximal 151 (often adapted to penetrate its cartridge septum when the assembly is attached to the drug delivery device. In the initial position, the proximal end of the needle is closed by a proximal septum 134 (referred to as the “back needle”). The distal portion 152 of the proximal hollow needle is sealingly received within the piston lumen using an internal constriction 153 (alternatively, an elastic seal member can be placed at the proximal end of the lumen. ), Thereby sealing the fluid communication with the piston lumen during the axial movement of the piston from the initial proximal position of the piston to the fully actuated distal position (see below). The septum 126 forms a partition between the interior of the proximal hollow needle and the interior of the reservoir.

  The distal needle assembly 140 is in sliding and frictional engagement with a needle carrier 141 having a distally directed contact surface 142 adapted to engage the user's skin surface, and the outer skirt 115. A proximally extending circumferential skirt portion 143, in a sliding and frictional engagement with the tubular portion 114, and a central lumen in which the distal hollow needle 145 is fixedly disposed The distal hollow needle 145 includes a proximal portion 146 adapted to penetrate the reservoir septum 113 and project into the reservoir, although initially In position, the proximal end of the needle is located distal to the septum. A needle cover 149 (see FIG. 4A) is initially attached to the distal end of the housing to cover the needle and needle carrier.

  In the embodiment of FIG. 2, the housing is made (or coated) from a polymeric material so that the inner surface portion of the housing is allowed to contact the liquid formulation for a period corresponding to the intended shelf life of the assembly. Is done. Alternatively, the housing may be made entirely or partially from glass. Correspondingly, FIG. 3 shows an alternative embodiment in which the housing 110 is replaced by a glass vial and the front and rear housing parts are changed.

  More specifically, FIG. 3 shows a drug delivery assembly 300 comprising a glass vial 310 having a piston 320, a front portion 360, and a rear portion 370, the front and rear portions being the embodiment of FIG. Bring the structure and function of the distal and proximal portions of the housing 110 to the glass vial. Apart from the modified piston and a portion of the front and rear parts that couple to the glass vial, the assembly of FIG. 3 is functionally identical to the assembly of FIG.

  The glass vial has a cylindrical main portion, a neck portion 311 having an outlet opening, a transition shoulder 312 between them, a partition wall 313 through which a needle can pass, and a partition wall in a sealing engagement state with the neck portion. A circumferential holding member 314. Piston 320 has a distal surface 322 adapted to accommodate the shoulder, thereby reducing dead space when the piston is moved fully forward to the neck volume. The anterior portion 360 is a lumen that includes a proximal lumen adapted to be attached to the neck of the vial, and a protrusion 361 adapted to engage the vial between the retaining member and the shoulder. It comprises. The rear portion 370 includes a circumferential distal groove 371 adapted to engage and grip the circumferential rear end of the glass vial.

  With reference to FIGS. 2 and 4A-4F, shown in FIG. 1 comprising a cartridge 161 filled with a medicament having a septum 163 through which a needle can penetrate and a hub mount 164 provided with a spring-driven release assembly. Although the use of the filled drug delivery assembly 100 in combination with the type of drug delivery device 160 will be described, the device may be of any suitable type, such as manual, spring or motor driven. In an exemplary embodiment, the delivery assembly comprises a (first) reservoir 105 containing a first drug in the form of a GLP-1 formulation, and the cartridge (representing a second reservoir) is in the form of an insulin formulation. Contains a second drug.

  4A and 5A show the initial assembly 100 with the needle cover 149 attached and the drive assembly 130 in a substantially non-biased state, with the distal opening of the proximal hollow needle 150 in the piston lumen. Placed and sealed, the drug reservoir is sealed by placing the proximal opening of the distal hollow needle 145 away from the reservoir septum.

  The user then aligns the delivery assembly with the hub mount 164 of the delivery device (see FIG. 4B), attaches the assembly to the device, for example using the illustrated screw or alternatively a bayonet connection, and removes the needle cover. For illustrative purposes, the coupling means of the device is not shown. As can be seen, when the assembly is attached to the device via the coupling means 119 that engages the hub mount 164, the back needle 151 passes through the proximal septum 134 and is inserted through the septum 163, and the interior of the cartridge 161. And the spring load member 131 is moved in the distal direction, thereby compressing the spring 132 toward the piston 120 which is held in place by the holding means and is stationary at this stage. Energize and pressurize reservoir. At this stage, the user can release the spring-driven release assembly of the delivery device, but since the distal outlet of the proximal needle is sealed inside the piston lumen, the drug from the delivery device can be removed at this stage. Not released (see FIGS. 4C and 5B).

  As a next step, when the user presses the distal contact surface 142 of the assembly against the skin surface with a moderate force, the pointed distal end of the distal needle 145 is inserted subcutaneously and the needle carrier 141 is against the assembly housing. The proximal portion 146 of the needle is then inserted through the reservoir septum 113 to establish fluid communication with the reservoir 105 (see FIG. 4D). As the reservoir septum is pierced, the piston retaining means is released and the spring 132 is extended, causing the piston to begin moving distally and releasing the drug from the assembly reservoir (see FIG. 4E). At this stage, the distal outlet of the proximal needle 150 is still sealed within the piston lumen 125, but if the drug in the device cartridge is pressurized just at this point, this pressure will also act on the piston. However, it is only extremely small because of the area of the lumen.

  When the piston is moved to the most distal position and the reservoir is ideally completely emptied, the proximal end of the distal needle 145 protruding into the reservoir passes through the piston septum 126 and then into the piston. Fluid communication is established between the distal needle 145 and the device reservoir 161 via the lumen and proximal needle (see FIG. 4F). As is apparent, the releasable holding means for holding the spring in a biased state is formed by a combination of a piston septum and an axially movable distal needle.

  If the delivery device is energized and released before the delivery assembly is activated, then the second medication will begin to be released from the cartridge 161. On the other hand, if the delivery device is manual, for example, the user can now start the injection manually, for example by depressing the injection button. Means may be provided in the assembly to generate an audible “click” sound to indicate that the reservoir is empty.

  In an alternative embodiment (not shown), the spring load can be eliminated, providing the user with an assembly in which the spring is pre-compressed and thus the reservoir is pressurized. In yet another alternative embodiment (not shown), the needle carrier (or “trigger member”) is automatically moved in the distal direction when the assembly is pulled back from the skin surface so that the needle is in the reservoir septum. The needle carrier can be spring-biased so that it is disengaged from the needle so that the injection stops (either the first or second drug).

  With reference to FIGS. 6A and 6B, a second embodiment of a filled drug delivery assembly 200 adapted to be used in combination with a drug delivery device 260 is described below, where the assembly is initially delivered to a user. Shown in state.

  The assembly includes a housing 210, an axially displaceable piston 220, a drive assembly 230, and an axially displaceable hollow needle 240. In the illustrated embodiment, the housing is made (or coated) from a polymeric material so that the inner surface portion of the housing is allowed to contact the liquid formulation for a period corresponding to the intended shelf life of the assembly. The Alternatively, the housing may be made entirely or partially from glass. The housing is assembled to a distal end 211 having a distal septum 212 with an axial lumen through which a pointed distal needle 241 is disposed and protrudes, and a corresponding hub mount as shown, for example, in FIG. And a proximal end with a tubular hub portion 213 provided with coupling means 214 (e.g. internal threads or bayonet as shown). In the illustrated embodiment, the pointed proximal needle portion 242 initially protrudes from the hub portion. The piston 220 is formed of a main portion 221 formed of a first elastic material that forms a sealing portion between the piston and the inner surface portion of the housing, and a second elastic material, and the needle 240 is slid and sealed. A central septum 222 having an axial lumen disposed therethrough in a stationary engagement. Alternatively, the piston may be formed from a single elastic material. A cylindrical release member 225 is attached to the piston and projects proximally therefrom and includes a circumferential proximal rim portion 226. When the piston is in the initial position, a reservoir 215 is formed between the piston and the housing and is filled with a liquid formulation. The drive assembly 230 comprises a retaining member 231 and a biasing means in the form of a spring 238, the spring having a proximal end supported by the housing and a distal end applying a force to the proximal end of the retaining member. Have. The holding member has a generally tubular shape and its distal end is initially located at a distance from the proximal end face of the piston main part, the holding member extending in the axial direction and facing two flexible locking arms 232 (see FIG. 6B), each having a free proximal end with a lateral projection 233 disposed on the inner surface of the housing and initially adapted to engage a proximally facing support structure 216. Have. In the illustrated embodiment, the proximally facing support structure 216 is in the form of an inner circumferential rim. The contact surface between the side projection and the support structure is inclined in the axial direction, so that the spring force acting on the holding member creates an inward force on the flexible arm. The flexible arm is disengaged from the support structure. However, in the initial state, the proximal rim portion 226 of the release member 225 is arranged to support the proximal end of the flexible arm, thus initially preventing the arms from disengaging from their support, The retaining member is prevented from moving distally by extension of the spring. As can be seen, the holding member, release member, and support structure work together as a holding means that initially holds the spring in a biased state. The hollow needle 240 is disposed in the vicinity of the distal portion 241 and the proximal portion 242, the intermediate opening 243 initially disposed in the closed and sealed position inside the piston partition member 222, and the tubular hub portion. A proximal collar member 244 adapted to engage the needle hub mount of the delivery device. The housing may be provided with a stop structure (not shown) that restrains distal movement of the needle collar member and proximal movement of the piston. The illustrated assembly 200 is supplied to the user in a sterilized condition enclosed in an external container (not shown).

  Referring to FIGS. 6A and 7A-7D, a filled drug in combination with a drug delivery device 260 of the type shown in FIG. 1 comprising a cartridge 261 filled with the drug and provided with a spring-driven release assembly. The use of the delivery assembly 200 is described. In an exemplary embodiment, the delivery assembly comprises a (first) reservoir 215 containing a first drug in the form of a GLP-1 formulation, and the cartridge (representing the second reservoir) is in the form of an insulin formulation. Contains a second drug.

  FIG. 7A shows the initial assembly 200 with the drive assembly locked and the needle intermediate opening 243 positioned and sealed within the piston lumen to form a sealed drug reservoir. A gap is provided between the piston and the holding member.

  When the assembly is attached to the hub mount 264 of the drug delivery device (either by screw coupling or bayonet coupling), the pointed proximal end 242 of the hollow needle 240 is inserted through the cartridge septum 263. During the coupling operation, the distal end of the hub mount engages the needle collar member 244 and pushes the needle axially, causing the intermediate opening 243 to move out of engagement with the piston, Located at the proximal end, fluid communication is created between the reservoir and the cartridge, between the reservoir and the distal needle, and thus between the cartridge and the distal needle (see FIG. 7B). At this point, there is virtually no drug flow.

  Once the user has loaded the spring-driven release assembly by setting the drug delivery device to the desired dose, the combination assembly (ie, filled drug delivery assembly 200 and drug delivery device) is ready for use. Accordingly, after the user inserts the needle subcutaneously, when the spring is released by activating the drug delivery device, liquid drug passes from the cartridge through the hollow needle 240 and distally inserted into the intermediate opening 243 and subcutaneously. Extruded through both ends. However, since the opening is designed to have a much smaller flow resistance than the downstream portion of the hollow needle, the majority of the drug that was initially released from the cartridge is pushed into the reservoir and directed proximally to the piston. Apply the power you had. As a result, the piston including the release member 225 moves in the proximal direction, and the rim portion 226 moves to disengage from the support engagement with the locking arm 232. At the same time, the proximal surface of the piston moves to contact the distal end of the retaining member. The housing includes a protrusion (not shown) that engages the proximal end of the retaining member in the initial position so that the retaining member and the piston do not move further in the proximal direction. As described above, when the locking arm is no longer prevented from moving inward, the spring force acting on the retaining member creates an inward force on the flexible arm, which causes the flexible arm to engage the support. The piston is moved forward by the spring 238 by the holding member, and the medicine is released from the reservoir 215.

  At the same time, however, the piston is exposed to a proximally directed pressure by the liquid in the reservoir, corresponding to the pressure generated by the spring of the drug delivery device (lower by the pressure drop in the needle). If the force on the piston due to the pressure in the reservoir generated by the spring of the device is greater than the force exerted on the piston by the spring 238 of the assembly, until the set dose is completely released from the drug delivery device and delivered through the needle The piston does not move forward. During this operation, substantially no drug flows through the intermediate opening 243. When the release of the drug from the cartridge is complete, the pressure in the reservoir is reduced, allowing the assembly spring to move the piston forward, and the drug is released from the reservoir through the intermediate opening 243 (FIGS. 7C and 7D). reference). At this point, both doses of drug have been released through a common delivery needle.

  Conversely, if the force on the piston due to the pressure in the reservoir generated by the device spring is less than the force exerted on the piston by the assembly spring 238, the piston will first release the needle completely from the assembly reservoir. Until it is delivered through, after which the drug is released from the cartridge. In practice, it is necessary to prevent the drug from flowing backwards into the cartridge from the assembly reservoir through the intermediate opening, but spring-driven drug delivery devices in most cases are unidirectional cups that prevent the piston rod from being pushed back. Since it has a ring (eg FlexTouch® by Novo Nordisk), this is not a problem. When the drug release from the reservoir is completed in this way, the pressure in the reservoir decreases and the spring of the device can move the piston forward, and then the set drug dose is transferred from the cartridge through the needle. Released. Alternatively, a valve for controlling the direction of flow may be provided in the flow conduit of the delivery assembly.

  During this operation, substantially no drug flows through the intermediate opening 243. When the release of the drug from the cartridge is complete, the pressure in the reservoir is reduced, allowing the assembly spring to move the piston forward, and then the drug is released from the reservoir through the intermediate opening 243. At this point, both doses of drug are released through a common delivery needle and substantially no drug remains in the delivery assembly.

  As will be apparent, for a delivery system that combines a delivery assembly 200 pre-filled with a first medication and a medication delivery device 260 filled with a second medication, the components (eg, spring and flow characteristics) are It can be designed to release either the first or second drug first. In fact, the system can be designed to deliver both drugs substantially simultaneously. Depending on the properties of the two drugs and their formulation, the order in which they are injected can affect pharmacokinetics, such as blood absorption.

  FIG. 8 illustrates a third pre-fill delivery assembly 400 comprising a polymer housing 410, an axially displaceable piston 420, and a drive assembly (not shown but corresponding to drive assembly 230 described above). An embodiment is shown schematically. When the piston is in the initial position, a reservoir 415 is formed between the piston and the housing and is filled with a liquid formulation. The housing includes a distal hollow needle 441 in fluid communication with the reservoir, a proximal hollow needle 442 adapted to engage a cartridge septum of the drug delivery device, a proximal needle formed in the housing wall, A conduit 411 in fluid communication with the reservoir, the conduit having an opening 412 at the distal-most end of the reservoir. The reservoir is provided to the user in a sealed state, for example by sealing both needle ends by suitable means that are removed when the assembly is removed from the protective packaging prior to use.

  In use, the third embodiment works substantially the same as the first embodiment when the single hollow needle of the first embodiment is moved forward, the difference being the drug delivery device The fluid communication between the cartridge and the reservoir of the assembly is formed through a conduit 411 rather than a displaceable hollow needle 240. In yet another embodiment (not shown), the assembly can be provided with manually releasable locking means.

  The exemplary embodiments disclosed above can be modified and added features to further improve the user experience. For example, a dedicated display device, such as a visual display that changes color, for example, indicating whether the assembly is operating, even though the piston is at its distal position, indicating that the assembly has been used up Can be provided. For example, by placing a color mark on the housing, eg, a holding member that moves axially during operation, the first color is shown when the assembly is in the initial state, and the assembly is activated and the piston is moved to the distal position. A window showing the second color can be provided. Means may be provided in the assembly to generate one or two audible “click” sounds to indicate that the assembly has been activated and / or that the reservoir has been emptied.

  The delivery assembly may be provided with a sliding needle protector that initially covers the distal needle so that the needle protector is pushed proximally when the assembly is pressed against the skin surface. The needle protector can be spring biased so that when the assembly is pulled back from the skin surface, it automatically moves in the distal direction to cover the distal needle. The needle protector can also be used to form a lock such that the assembly cannot be released until the needle protector is pushed proximally. With respect to the design corresponding to the embodiment of FIG. 6, this allows the user to “empty” or allow air to escape from the needle prior to inserting the distal needle subcutaneously. In an integrated system, the axial movement of the needle protector can be used to release the drive mechanism of the drug delivery device.

  In the above description of the preferred embodiments, various structures and means for implementing the functions described for the various components have been described to the extent that the spirit of the invention becomes apparent to those skilled in the art. Detailed configurations and specifications for the various components should be considered the goals of a standard design process performed by those skilled in the art along the lines described herein.

Claims (15)

A housing (110, 210, 310, 410);
A piston (120, 220, 420) capable of axial displacement within the housing from an initial position;
A variable volume reservoir (105, 215, 305, 415) formed by the housing and the piston and initially containing a fluid medicament;
An external fluid inlet (150, 242, 350, 442) disposed in fluid communication with the reservoir or configured to be disposed in fluid communication;
A fluid outlet (145, 241, 345, 441) arranged in fluid communication with the reservoir or configured to be placed in fluid communication;
A deflection means (130, 230, 330) configured to move the piston forward;
-Releasable holding means (113, 226, 231, 313) configured to hold the biasing means in a biased state;
When the holding means is released, the biasing means in the biased state can move the piston forward to release the fluid medicine from the reservoir.
Drug delivery assembly (100, 200, 300, 400).   The drug delivery assembly according to claim 1, wherein the biasing means (130, 330) is configured to be moved from an initial state to a biased state by a user operation. A drug delivery assembly configured to be attached to a drug delivery device (160) comprising:
First coupling means (119)
Further comprising
The drug delivery device comprises:
-A second reservoir (261) containing a second fluid medicament;
-Second coupling means (164) configured to attach to said first coupling means;
When the first coupling means and the second coupling means are coupled together, the fluid inlet is disposed in fluid communication with the second reservoir, and the displacement means is moved from the initial state to the Moved to the energized state,
The drug delivery assembly of claim 2. The fluid outlet is biased by an initial state where there is no fluid communication between the fluid outlet and the reservoir, and when there is fluid communication between the fluid outlet and the reservoir; An actuating state that allows the positioning means (130) to move the piston (120) forward to release fluid medication from the reservoir through the fluid outlet;
The fluid inlet has an initial state in which there is no fluid communication between the fluid inlet and the reservoir, and an operating state in which fluid communication exists between the fluid inlet and the fluid outlet;
4. A drug delivery assembly according to any one of claims 1 to 3.   The piston comprises a fluid conduit (125) in fluid communication with the fluid inlet, the piston from the initial position where there is no fluid communication between the fluid conduit and the fluid outlet; 5. A drug delivery assembly according to claim 4, wherein the drug delivery assembly is movable to a connection position where fluid communication is formed between the fluid conduit and thus between the fluid inlet and the fluid outlet. The reservoir comprises an area (113) through which the needle can penetrate;
The fluid outlet is a distal hollow needle (145) that is axially displaceable between an initial position and an operating position, wherein there is fluid communication between the fluid outlet and the reservoir in the initial position; Without taking the form of a distal hollow needle (145) in which the distal hollow needle is placed in fluid communication with the reservoir by being disposed through the needle penetrable region in the activated position;
The biasing means in the biased state allows the piston to move forward to release fluid medicament from the reservoir through the distal hollow needle;
6. A drug delivery assembly according to claim 4 or 5. The proximal portion (146) of the distal hollow needle protrudes into the reservoir at the activated position of the distal hollow needle;
The piston comprises a region (126) through which the needle can penetrate;
A proximal hollow needle, wherein the fluid inlet has a distal portion disposed in the piston conduit and is in fluid communication with the piston conduit when the piston moves axially from its initial position to its connected position ( 150), wherein in the connected position, the proximal portion (146) of the distal hollow needle is disposed through the needle penetrable region (126) of the piston to provide fluid flow with the proximal hollow needle. In the form of a proximal hollow needle (150), in communication,
Fluid communication is formed between the distal hollow needle and the proximal hollow needle via the piston conduit;
The drug delivery assembly of claim 6. A medical assembly comprising a drug delivery assembly (100) and a drug delivery device (160) according to any one of the preceding claims, wherein the drug delivery assembly comprises:
First coupling means (119)
Further comprising
The drug delivery device comprises:
-A second reservoir (161) containing a second fluid medicament;
A release assembly configured to release a dose of drug from the second reservoir;
-Second coupling means (164) configured to attach to said first coupling means;
When the first coupling means and the second coupling means are coupled together, the fluid inlet (151) is disposed in fluid communication with the second reservoir;
Medical assembly.   The drug delivery assembly according to claim 1 or 2, wherein the retaining means (231) is configured to be released when fluid is introduced through the fluid inlet.   10. A drug delivery assembly according to claim 9, wherein the retaining means is released by moving the piston backward by fluid introduced into the reservoir via the fluid inlet. -A proximal end forming said fluid inlet;
-A distal end forming said fluid outlet;
The medicament according to claim 9 or 10, further comprising a hollow needle (240) having an intermediate opening (243) disposed in fluid communication with the reservoir or configured to be disposed in fluid communication. Delivery assembly.   The hollow needle is disposed through the piston, the piston is configured to move axially rearward and forward with respect to the hollow needle, and a sealing portion (222) includes the piston and the hollow needle. 12. A drug delivery assembly according to claim 11 provided between the two.   The hollow needle has an initial position and an operating position, where the intermediate opening is disposed in sealing engagement with the piston, and in the operating position, the intermediate opening is in fluid communication with the reservoir. The drug delivery assembly of claim 12, wherein 14. A drug delivery assembly according to claim 12 or 13, wherein the drug delivery assembly is adapted to be attached to a drug delivery device (260).
First coupling means (214)
Further comprising
The drug delivery device comprises:
-A second reservoir (261) containing a second fluid medicament;
-Second coupling means (264) configured to attach to said first coupling means;
When the first coupling means and the second coupling means are coupled together, the fluid inlet is disposed in fluid communication with the second reservoir, and the hollow needle moves to its operating position;
Fluid communication (243) is established between the second reservoir and the reservoir of the drug delivery assembly and between the reservoir of the drug delivery assembly and the fluid outlet;
Drug delivery assembly.   The drug delivery assembly of claim 1, further comprising user-actuated release means configured to release the retaining means when actuated.

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